Nanotech Pioneer Langer Wins Award by Thinking Small

M.I.T.’s Robert Langer is being recognized for his efforts to fight cancer and other diseases by melding nanoscale engineering with science and medicine

February 10, 2015 |By Larry Greenemeier

Scientific American spoke with M.I.T.’s Robert Langer shortly after he was named as the recipient of this year’s Queen Elizabeth Prize for Engineering.Courtesy of the 2015 Queen Elizabeth Prize for Engineering.

Bioengineer Robert Langer has spent his career looking for the next not-so-big thing. He’s had much success thinking small, pioneering breakthroughs in nanoscale medicine to fight cancer, administer drugs with precision and replace damaged tissue. These and his various other achievements received recognition from across the Atlantic last week [on February 3] when Langer was awarded the £1-million (roughly $1.5-million) 2015 Queen Elizabeth Prize for Engineering. Previous recipients of the prize include Tim Berners-Lee and other co-creators of the World Wide Web.

Langer’s path through chemistry, engineering, medicine and entrepreneurship began more than four decades ago working with biomedical researcher, the late Judah Folkman, on a breakthrough that helped isolate the first substances that blocked cancerous tumor angiogenesis (the formation of new blood vessels). He later pioneered the development of polymer vessels that control the release of large molecular weight drugs used in the treatment of cancer and mental illness.

His collaboration with pediatric surgeon Joseph Vacanti at Massachusetts General Hospital helped create synthetic polymers that could deliver cells to form specific tissue structures. This advance led to the development of a new kind of artificial skin, now approved by the U.S. Food and Drug Administration for use on burn victims and patients with diabetic skin ulcers.

One of Langer’s most high-profile projects in recent years has been his work on a remote-controlled drug delivery microchip. The chip can be implanted under the skin near the abdomen or backside and is designed to store and release precise doses of a drug on demand or at scheduled intervals for up to 16 years. He co-founded a start-up called Microchips Biotech to commercialize the technology, starting with a system that enables women to regulate their fertility. The hormones are housed inside a platinum and titanium seal, which can be broken using a single electrical current to distribute the hormone. Clinical trials of the contraceptive microchip are scheduled for 2016.

Langer is currently the David H. Koch Institute Professor at the Massachusetts Institute of Technology and a member of Scientific American’s Board of Advisers. The native of Albany, N.Y., has also served as a member of the FDA’s Science Board, the agency’s highest advisory board. He chaired the board from 1999 to 2002.

Scientific American spoke with Langer shortly after he was named as the recipient of this year’s Queen Elizabeth Prize for Engineering.

[An edited transcript of the interview follows.]

Are you excited to meet the queen of England? [laughs] I’ve met some presidents and some kings but never the queen of England. That’ll be a lot of fun. Prince Andrew was at the event in London on [February 3] to announce the award. To me it’s just very nice and a tremendous honor that people are giving me this. I guess I will get to see how Buckingham Palace compares to the White House.

What originally led you to hypothesize that large molecules used in cancer and diabetes treatments could pass through a polymer membrane, particularly when it seems no one else was doing this? Some of it probably was my naiveté. I didn’t know what could be done or what couldn’t be done. I hadn’t read the literature that said it was impossible to do. I’d love to give you an explanation like I had this great theory—and I did have some theories. I was just 25 years old and thought lots of things must be possible. I experimented with hundreds of different techniques. So some of it was Edisonian. And it was sort of a serendipitous discovery. I think I did have in the back of my mind, although this is a little hard to remember from 41 years ago, the type of thing that eventually did turn out to be tiny, complex, tortuous, porous pathways—that that might be something that could be done.

Mostly I just remember being curious and experimenting with different things. I really wanted to solve this because I wanted to isolate this angiogenesis inhibitor. That was my job as a postdoctoral fellow with Judah Folkman. I felt like if I couldn’t do that, I couldn’t develop this bioassay to study angiogenesis. I needed to be able to slowly release molecules the size of angiogenesis inhibitors for weeks to develop that bioassay in order to study the blood vessel growth and isolate the first angiogenesis inhibitor—that was what was driving the whole thing. It wasn’t about [treating] a particular disease in the beginning.

You’ve done so much to develop tiny containers that enable the timed release of large-molecule drugs. What are your thoughts related to the propulsion and navigation needed to get those containers to the right spot in the body? We’ve tried to do it more by making a container with the right surface chemistry that will avoid macrophages [that attack foreign substances in the body] and that will target to the right cells. The approach you take depends on what you want to do. We’ve also used magnetism and ultrasound to control the movement of substances injected into the body. Working with my former postdoc Joseph Kost [now dean of engineering at Ben-Gurion University in Israel], we studied magnetism in particular to get drugs to pass through the pores in their polymer containers.

My feeling in terms of practical use is to do things [more simply]. For example, if you can decorate the materials well enough to create the surface chemistry that gets them to the right place, that will be better from a safety standpoint. Then the question is: Will that be good enough in terms of efficacy?

You’ve also worked with colleagues on technologies designed to administer drugs such as insulin using a swallowed capsule rather than an injection. How far along is this work and how does it tie into your work with timed-release polymers? That technology is being developed by a company called Entrega, which is based on a technology developed by one of my former students, Samir Mitragotri [now a chemical engineering professor at the University of California, Santa Barbara], and a former postdoc, Kathryn Whitehead [currently an assistant professor at Carnegie Mellon University], who worked with me. I’m chairman of the scientific advisory board. The technology is in animal trials but it’s going well.

The key issues they’re working on now are increasing the bioavailability and testing on larger and larger animals. By bioavailability, I mean when I give you a drug, let’s say orally, how much actually gets into the bloodstream? If you inject it intravenously, 100 percent gets in. But one of the issues, particularly with a large-molecule drug, is that smaller amounts will get in. That’s what Entrega is hoping to address.

The Gates Foundation has been a large source of funding for Microchips, last year awarding the start-up$4.6 million in fundingto further its development of a personal system that enables women to regulate their fertility. What is the status of this project? There have been two grants for this work from the Gates Foundation for more than $6 million, and I think there’ll be a third one soon. The microchips are being developed, although they’re not approved yet. There’s been really good progress, they’re working on the design of the system, the release kinetics of the system, animal tests and stability formulation.

I suppose the biggest challenge is getting the kinetics the right way. [Each implantcontains 200 microreservoirs—small, hermetically sealed drug compartments—each of which holds up to one milligram.] You want each reservoir to release for 30 days theoretically. And you want to do this using a device that’s as small as possible, as cheap as possible and can pack in as much drug as possible. When you do that, can you make sure that each reservoir in the chip, for example, releases the drug at an absolutely constant rate over a month until all of the drug is gone? That might mean that your chip has to be a little bigger, so you’re wrestling with those kinds of issues.

Regarding the microchip-based implants, are you able to communicate with them once they are implanted or do they have to be preprogrammed before the procedure? You could preprogram it—there is a little computer program in the device’s chip. If you use an active chip, you could also send it a signal that changes the program. There could be all kinds of bells and whistles with that approach to make sure there are encryption and other security. In a paper in Nature with [M.I.T. engineering professor] Michael Cima and our student John Santini we described how we sent a signal to a chip that removes the reservoir cap in a controlled, precise way, perhaps like a fuse blowing off in a controlled way. This type of chip is currently in human trials and has proven to be very safe and effective thus far. [Scientific American is part of Nature Publishing Group.]

We also published in Nature Materials a method of using what I call a passive chip, where the chip is preprogrammed and totally biodegradable. The casing will dissolve based on the polymer you use, a process you can regulate by changing the molecular weight of the polymer.

In addition to regulating fertility, how might this technology be used to treat other conditions? You might also want the microchip to administer multiple drugs to create a combination therapy for cancer, for example, using the anticancer treatments BiCNUand Temodar. You would program the chip to release each drug at a specific time interval, almost like personalized medicine. We’re also looking at the chip as a way to administer medicine to people with osteoporosis or diabetes. Vaccines are another possibility, depending on the cost. Some people have approached us about delivering multiple types of RNAi [RNA interference] as ways of shutting down certain genetic pathways. These are not in clinical trials, but some version will be someday, whether it’s us or somebody else.

Given your background as a former chairman of the FDA’s Science Board, who do you think would be a good choice to spearhead Pres. Obama’s newPrecision Medicine Initiative? I think the person has to be a great scientist, with a clinical background, and a really good leader. When I look back at good leaders in government projects, certainly a terrific example of somebody that I think did a great job heading up the National Institutes of Health is [National Cancer Institute Director] Harold Varmus. He’s very smart, thoughtful and a visionary. There are others, too, but I think that when I look back at people who’ve been really good government people, people like Harold—Tony Fauci, director of the National Institute of Allergy and Infectious Diseases (NIAID), is another good example—it’s finding people in medical centers and hospitals who are really outstanding researchers but who also have very good leadership skills.

Getting back to your time with the FDA, to what extent does that agency consider its advisory boards’ recommendations, and how can it make better use of their knowledge? Certainly when I was there from 1995 to 2002 I thought they made very good use of the science board. In fact, they had all the heads of the major divisions come to the meetings, so I think they took it very seriously. We wanted to make the science they were using as modern and up-to-date as possible. Sometimes we’d bring outside people in to talk about new scientific advances, and I think they welcomed that.

Your career has taken on a path that includes engineering, biochemistry, materials science and business/entrepreneurship. Would you recommend this type of interdisciplinary path for current students interested in science, technology, engineering and math (STEM)—and why? People end up learning by doing, so you just want to create opportunities for them. I still feel the number-one thing to do is to learn fundamentals. And then I think you want to follow your passion—whatever your passion is, that’s what you should do. I don’t think there’s any specific formula or any specific one thing that somebody has to do. Learn the fundamentals, follow your heart, find something you really love and then go to work.